Phorbol 12-myristate 13-acetate induces senescence of HL-60 leukemic cells
2018
Authors:
Mandić, MilošVučićević, Ljubica
Misirkić Marjanović, Maja
Jovanović, Maja
Harhaji-Trajković, Ljubica
Trajković, Vladimir
Contributors
Đorđević, AnaDocument Type:
Conference object (Published version)
,
© 2018 by the Institute for Biological Research “Siniša Stanković”, University of Belgrade
Metadata
Show full item recordAbstract:
Introduction: Phorbol myristate acetate (PMA) is in
clinical investigation for treatment of acute myeloid
leukemia due to its differentiating ability. Cell differentiation could be accompanied by senescence, a state
of irreversible cell cycle arrest.
Our aim was to investigate the ability of PMA to initiate
senescence in HL60 human leukemia cells.
Methods: Cell morphology was analyzed using phase
contrast microscopy. Cell cycle arrest was assessed
by flow cytometric analysis of propidium iodide stained
cells and BrdU colorimetric assay. Activity of senescence-associated beta-galactosidase (SA-βgal) was
assessed by cytochemical staining and flow cytometric analysis of fluorescein di-β-D-galactopyranoside
(FDG) stained cells. Senescence-associated gene expression of: cell cycle inhibitor p21, interleukin-8 (IL-8),
lamin B1 were quantified by RT-PCR, while activation
of NF-κB, main regulator of senescence associated secretory phenotype, was examined by immunoblotting.
Results: After the PMA treatment HL60 were enlarged and flattened with cytoplasmic vacuoles resembling morphology of senescent cells. Block in
leukemia cell proliferation in G1 phase was accompanied with increase in expression of cell cycle inhibitor p21 in PMA treated cells. Finally, PMA stimulated
SA-βgal activity, expression of genes responsible for
senescence associated secretory phenotype, NF-κB
and IL-8, while downregulating Lamin B1 expression.
Conclusion: Our results suggest that in addition to
PMA-induced cellular differentiation, senescence
participates in its previously shown cytostatic effect,
further supporting its investigation as a potential antileukemic drug.
Funding / projects:
- Modulation of intracellular energy balance-controlling signalling pathways in therapy of cancer and neuro-immuno-endocrine disorders (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41025)
- The role of autophagy in regulation of cancer cell death (RS-MESTD-Basic Research (BR or ON)-173053)
In:
- Đorđević A, editor. Program & Book of Abstracts. IUBMB Advanced School Nutrition, Metabolism and Aging; 2018 October 15-19; Petnica, Serbia. Belgrade : Institute for Biological Research "Siniša Stanković"; 2018. p. 38.